While the PI and others in the field have demonstrated a requirement for altered intracellular calcium levels in the regulation of apoptosis, little data are available regarding the intracellular targets for this factor. A calcium regulated protease has been identified by the PI from the nucleus that appears to be required for both lamin B degradation and DNA fragmentation. The PI has also demonstrated that there is a caspase cleavage consensus sequence in the IP3 receptor. This proposal is designed to: 1) identify the calcium-activated protease required for thymocyte apoptosis; 2) determine if the anti-apoptotic protein bcl-2 regulates this proteases and 3) determine if the type 1 IP3 receptor is required for apoptosis.